Publications by authors named "Reginald Atkins"

3 Publications

  • Page 1 of 1

Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma.

Blood 2021 May;137(19):2621-2633

Department of Blood and Marrow Transplant and Cellular Immunotherapy.

Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated whether immune dysregulation, present before CAR T-cell therapy, was associated with treatment failure. Tumor expression of interferon (IFN) signaling, high blood levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and high blood interleukin-6 and ferritin levels were each associated with a lack of durable response. Similar to other cancers, we found that in LBCL tumors, IFN signaling is associated with the expression of multiple checkpoint ligands, including programmed cell death-ligand 1, and these were higher in patients who lacked durable responses to CAR-T therapy. Moreover, tumor IFN signaling and blood M-MDSCs associated with decreased axi-cel expansion. Finally, patients with high tumor burden had higher immune dysregulation with increased serum inflammatory markers and tumor IFN signaling. These data support that immune dysregulation in LBCL promotes axi-cel resistance via multiple mechanistic programs: insufficient axi-cel expansion associated with both circulating M-MDSC and tumor IFN signaling, which also gives rise to expression of immune checkpoint ligands.
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http://dx.doi.org/10.1182/blood.2020007445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120145PMC
May 2021

Impedance spectroscopy as an indicator for successful in vivo electric field mediated gene delivery in a murine model.

Bioelectrochemistry 2017 Jun 27;115:33-40. Epub 2017 Jan 27.

Department of Chemical and Biomedical Engineering, University of South Florida, 4202 E. Fowler Ave. ENB 118, Tampa, FL 33620, USA; Center for Molecular Delivery at USF, University of South Florida, 4202 E. Fowler Ave. ENB 118, Tampa, FL 33620, USA.

In vivo gene electro transfer technology has been very successful both in animal models and in clinical trials over the past 20years. However, variable transfection efficiencies can produce inconsistent outcomes. This can be due to differences in tissue architecture and/or chemical composition which may effectively create unique biological environments from subject to subject that may respond differently to the identical electric pulses. This study investigates the integration of impedance spectroscopy into the gene electro transfer process to measure murine skin impedance spectra before, during (after pulse delivery), and after gene electro transfer pulse application to determine if changes in impedance correlate with reporter gene expression. Both post-treatment impedance spectra and gene expression were dependent upon the applied electric field strength. These results indicate that alterations in tissue impedance produced by the applied electric field represent an excellent parameter to predict degrees of transfection and gene expression. These results could ultimately be used to alter pulsing parameters in order to optimize delivery/expression.
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http://dx.doi.org/10.1016/j.bioelechem.2017.01.004DOI Listing
June 2017

Direct Current Helium Plasma for Delivery of Plasmid DNA Encoding Erythropoietin to Murine Skin.

Plasma Med 2017 ;7(3):261-271

Dept of Chemical and Biomedical Engineering, University of South Florida, College of Engineering, Tampa, FL.

The use of electric fields to deliver DNA, called electroporation, has the potential to broadly impact vaccination and disease treatment. The evidence for this has emerged from a large number of recently completed and ongoing clinical trials. The methods for applying electric fields to tissues traditionally involve contact between metal electrodes and the tissue. In this study, we investigated the use of helium plasma as a noncontact method for electrically treating tissue in a manner that results in the uptake and expression of foreign DNA in murine skin. More specifically, our goal was to demonstrate that DNA encoding a model-secreted protein could be delivered, detected in the blood, and remain functional to produce its known biological effect. Murine erythropoietin (EPO) was the model-secreted protein. Results clearly demonstrated that an intradermal DNA injection followed by plasma treatment for 2 min resulted in elevated levels of EPO in the blood and corresponding hemoglobin increases that were statistically significant relative to DNA injection alone.
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http://dx.doi.org/10.1615/PlasmaMed.2017019506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404545PMC
January 2017